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Calcium Carbonate versus Sevelamer Hydrochloride as Phosphate Binders after Long-Term Disease Progression in 5/6 Nephrectomized Rats

DOI: 10.1155/2014/538392

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Abstract:

Our aim was to compare the effects of calcium carbonate and sevelamer-HCl treatments on calcium-phosphate metabolism and renal function in 5/6 nephrectomized (NX) rats so that long-term disease progression preceded the treatment. After 15-week progression, calcium carbonate (3.0%), sevelamer-HCl (3.0%), or control diets (0.3% calcium) were given for 9 weeks. Subtotal nephrectomy reduced creatinine clearance (?40%), plasma calcidiol (?25%), and calcitriol (?70%) and increased phosphate (+37%), parathyroid hormone (PTH) (11-fold), and fibroblast growth factor-23 (FGF-23) (4-fold). In NX rats, calcium carbonate diet increased plasma (+20%) and urinary calcium (6-fold), reduced plasma phosphate (?50%) and calcidiol (?30%), decreased creatinine clearance (?35%) and FGF 23 (?85%), and suppressed PTH without influencing blood pH. In NX rats, sevelamer-HCl increased urinary calcium (4-fold) and decreased creatinine clearance (?45%), PTH (?75%), blood pH (by 0.20 units), plasma calcidiol (?40%), and calcitriol (?65%). Plasma phosphate and FGF-23 were unchanged. In conclusion, when initiated after long-term progression of experimental renal insufficiency, calcium carbonate diet reduced plasma phosphate and FGF-23 while sevelamer-HCl did not. The former induced hypercalcemia, the latter induced acidosis, while both treatments reduced vitamin D metabolites and deteriorated renal function. Thus, delayed initiation influences the effects of these phosphate binders in remnant kidney rats. 1. Introduction Cardiovascular disease is a major cause of mortality in chronic renal insufficiency (CRI) with a 20-fold increase in the risk of cardiovascular death compared with normal population [1]. Hyperphosphatemia and secondary hyperparathyroidism (SHPT) [2] significantly contribute to the cardiovascular pathology and mineral-bone disorders in CRI. In order to halt these changes, oral phosphate binders such as calcium carbonate and sevelamer are widely used. High intake of calcium carbonate may predispose to vascular calcifications in CRI, especially if the phosphate levels remain inappropriately high [2]. Consequently, treatment with sevelamer, a calcium- and aluminium-free and nonabsorbable polyallylamine anion exchange resin, may result in less vascular calcifications and reduced mortality in dialysis patients. However, according to recent Cochrane review, the superiority of sevelamer over calcium carbonate remains unclear [3]. In experimental animal models, increased calcium intake has resulted in beneficial effects on blood pressure (BP), endothelial function,

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